NHLBI Working Group on Advancing the Science of Myocardial Recovery with Mechanical Circulatory Support

June 2 - 3 , 2016
Bethesda, MD


The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016, in Bethesda, Maryland to assess the state of the field and to identify critical gaps in knowledge and areas of opportunity for research to advance the science of myocardial recovery with mechanical circulatory support (MCS) devices. The Working Group’s charge was to develop recommendations for the NHLBI which will advance the science of myocardial recovery with MCS to enhance its identification, realization, and long-term effectiveness as a therapeutic intervention.  This scientific program will also likely yield advances in device technology and management that reduce MCS-associated adverse events that favorably impact myocardial recovery.

Cardiac remodeling driven by excess pressure and volume load drives the vicious cycle of progressive myocardial dysfunction in chronic heart failure (HF). By providing significant volume and pressure unloading and increased cardiac output, MCS devices allow a reversal of stress-related compensatory responses of the overloaded myocardium and, as a result, a subset of patients placed on long-term MCS can achieve variable degrees of improvement of the native heart structure/function and reversal of the systemic HF phenotype. 

Members of the Working Group provided short summaries of critical gaps of knowledge in the field, including the genetic, molecular, cellular, physiologic, and engineering aspects of myocardial recovery. Working Group members outlined specific opportunities and challenges associated with current MCS devices with respect to device design and adverse events that impact myocardial recovery to stimulate hypothesis-driven novel basic, translational, and clinical investigations. Each session was followed by discussion and recommendations. A central point that emerged from these discussions was that the lessons we learn from the specific, tractable, and well-controlled MCS population (for whom we have access to serial function, tissue, and serum analyses) can and should be extrapolated to the broader HF population, especially the ability to identify and distinguish the molecular mechanisms that are associated with advanced heart failure that recovers structurally and functionally, from those associated with advanced heart failure that is end-stage and does not recover. These discoveries in this MCS population could lead to treatments and strategies applicable to all of the various stages and levels of severity of HF. 


The working group provided the following recommendations and specific examples for each to the NHLBI regarding areas of need and opportunity in the science and engineering of myocardial recovery associated with MCS.

  1. Explore mechanistic approaches at the genetic, molecular, cellular, microstructural, or physiological level to improve the understanding of myocardial recovery and develop novel interventions.
    1. Assess the incidence, completeness, and sustainability of recovery using integrated physiology.
    2. Determine and exploit the mechanistic link between alterations in MCS pressure-volume loading profiles associated with myocardial recovery (i.e., identify and optimize biomechanical loading regimens that predict or contribute to sustained myocardial recovery).
    3. Develop methodologies to follow and optimize sustained recovery in post-explant patients including novel imaging and sensor technologies.
    4. Identify associations between molecular, hematologic, and/or biochemical markers and hemodynamic/clinical parameters that: 1) define clinical recovery or 2) define maladaptive consequences during MCS.
    5. Interrogate genetic/genomic responses in recovery that may be relevant to the broader HF population.
  2. Utilize epidemiological approaches and population based studies to identify the associative host factors and MCS device characteristics that influence the incidence and degree of myocardial recovery associated with MCS.
    1. Distinguish between favorable and unfavorable host factors that affect recovery with MCS (i.e., age, sex, genetics, disease state, duration of HF, etc.).
    2. Identify the biological and clinical determinants of the degree and sustainability of recovery.
    3. Assess the degree and sustainability of recovery in HF populations receiving MCS and non-MCS interventions.
    4. Determine favorable and unfavorable device characteristics or clinical events related to devices that influence myocardial recovery (e.g., unloading characteristics, flow characteristics, the impact of MCS adverse events on recovery and understanding MCS effects on the cardiovascular system to reduce them).
  3. Leverage innovative strategies and approaches to investigate the science and engineering of myocardial recovery with MCS.
    1. ​Develop appropriate animal models for targeted mechanistic studies of myocardial recovery.
    2. Develop objective measures of unloading and reloading of myocardium using advanced imaging modalities and sensors, metabolic techniques, and physiological data.
    3. Develop novel MCS device designs and control strategies that could enhance myocardial recovery.
    4. Develop a bio-repository to implement high priority recommendations.
    5. Leverage existing networks (i.e., data sources such as clinical registries) to implement translational and/or clinical studies of recovery.
    6. Develop specialized expertise and infrastructure for preclinical testing of novel adjunctive therapies to promote myocardial recovery.
    7. Translate novel adjuvant interventions (shown in preclinical studies or human lab-based studies to enhance recovery) into clinical therapies through randomized clinical trials or other novel adaptive trial designs.

The Working Group recommended inclusion of adult and pediatric populations.  The research efforts should, when appropriate, include patient-reported outcomes and cost data to allow study of the effect of interventions aimed at recovery on quality-of-life and cost-effectiveness.

The Working Group also developed the following working definition of cardiac recovery

“A reversal of the pathological state of the myocardium with significant improvement in cardiac structure and function sufficient to achieve a sustained remission from the heart failure phenotype.”

Publication Plans:

A manuscript is planned for a peer-reviewed publication.